Dataset Information

Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression.

ABSTRACT: Coordinated gene transcript levels across tissues (denoted "gene synchrony") reflect converging influences of genetic, biochemical and environmental factors; hence they are informative of the biological state of an individual. So could brain gene synchrony also integrate the multiple factors engaged in neuropsychiatric disorders and reveal underlying pathologies? Using bootstrapped Pearson correlation for transcript levels for the same genes across distinct brain areas, we report robust gene transcript synchrony between the amygdala and cingulate cortex in the human postmortem brain of normal control subjects (n = 14; Control/Permutated data, p<0.000001). Coordinated expression was confirmed across distinct prefrontal cortex areas in a separate cohort (n = 19 subjects) and affected different gene sets, potentially reflecting regional network- and function-dependent transcriptional programs. Genewise regional transcript coordination was independent of age-related changes and array technical parameters. Robust shifts in amygdala-cingulate gene synchrony were observed in subjects with major depressive disorder (MDD, denoted here "depression") (n = 14; MDD/Permutated data, p<0.000001), significantly affecting between 100 and 250 individual genes (10-30% false discovery rate). Biological networks and signal transduction pathways corresponding to the identified gene set suggested putative dysregulated functions for several hormone-type factors previously implicated in depression (insulin, interleukin-1, thyroid hormone, estradiol and glucocorticoids; p<0.01 for association with depression-related networks). In summary, we showed that coordinated gene expression across brain areas may represent a novel molecular probe for brain structure/function that is sensitive to disease condition, suggesting the presence of a distinct and integrated hormone-mediated corticolimbic homeostatic, although maladaptive and pathological, state in major depression.

SUBMITTER: Gaiteri C

PROVIDER: S-EPMC2848620 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression.

Gaiteri Chris C Guilloux Jean-Philippe JP Lewis David A DA Sibille Etienne E

PloS one 20100401 4

Coordinated gene transcript levels across tissues (denoted "gene synchrony") reflect converging influences of genetic, biochemical and environmental factors; hence they are informative of the biological state of an individual. So could brain gene synchrony also integrate the multiple factors engaged in neuropsychiatric disorders and reveal underlying pathologies? Using bootstrapped Pearson correlation for transcript levels for the same genes across distinct brain areas, we report robust gene tra ...[more]

PMID: 20376317

Similar Datasets

Project description:Background: There is an urgent need for a meta-analysis that characterizes the brain states of major depression disorder (MDD) patients and potentially provides reliable biomarkers, because heterogeneity in the results of resting-state functional neuroimaging has been observed between studies, with some patients not showing the consistent changes, or even opposite patterns. Thus, we evaluated consistent regional brain activity alterations in medication-naive patients with first-episode unipolar MDD and compared the results with those in healthy controls (HCs). Methods: A systematic database search was conducted (in PubMed, Ovid, and Web of Knowledge) between January 1984 and July 2016 to select resting-state functional activity studies with a voxel-wise analysis in MDD. We used anisotropic effect size-signed differential mapping to perform a whole-brain meta-analysis, comparing functional alterations between first-episode medication-naive unipolar MDD patients and HCs by integrating the studies. In addition, subgroup meta-analysis was conducted to control for the MRI analysis method. Moreover, the meta-regression analyses were performed to examine the potential effects of mean age, education duration, illness duration, and severity of depressive symptoms. Results: A total of 12 studies were included, comparing 313 MDD patients with 283 HCs. The pooled and subgroup meta-analysis found that the MDD patients showed hyperactivity in the left parahippocampal gyrus, left supplementary motor area, left amygdala, left hippocampus, and left middle frontal gyrus (MFG; orbital part), and hypoactivity in the left lingual gyrus, left middle occipital gyrus, right cuneus cortex, right MFG (orbital part), and left cerebellum. In the meta-regression analyses, the mean illness duration was positively associated with hyper-activation in the left parahippocampal gyrus and hypoactivation in the hemispheric lobule IV/V of the left cerebellum. Conclusions: This meta-analysis indicated that MDD patients had significant and robust resting-state brain activity alteration in amygdala, left hippocampus and other regions, which implicated this finding in the pathophysiology of cognitive and emotional impairment in MDD patients.

Project description:Temporal neural synchrony disruption can be linked to a variety of symptoms of major depressive disorder (MDD), including mood rigidity and the inability to break the cycle of negative emotion or attention biases. This might imply that altered dynamic neural synchrony may play a role in the persistence and exacerbation of MDD symptoms. Our study aimed to investigate the changes in whole-brain dynamic patterns of the brain functional connectivity and activity related to depression using the hidden Markov model (HMM) on resting-state functional magnetic resonance imaging (rs-fMRI) data. We compared the patterns of brain functional dynamics in a large sample of 314 patients with MDD (65.9% female; age (mean ± standard deviation): 35.9 ± 13.4) and 498 healthy controls (59.4% female; age: 34.0 ± 12.8). The HMM model was used to explain variations in rs-fMRI functional connectivity and averaged functional activity across the whole-brain by using a set of six unique recurring states. This study compared the proportion of time spent in each state and the average duration of visits to each state to assess stability between different groups. Compared to healthy controls, patients with MDD showed significantly higher proportional time spent and temporal stability in a state characterized by weak functional connectivity within and between all brain networks and relatively strong averaged functional activity of regions located in the somatosensory motor (SMN), salience (SN), and dorsal attention (DAN) networks. Both proportional time spent and temporal stability of this brain state was significantly associated with depression severity. Healthy controls, in contrast to the MDD group, showed proportional time spent and temporal stability in a state with relatively strong functional connectivity within and between all brain networks but weak averaged functional activity across the whole brain. These findings suggest that disrupted brain functional synchrony across time is present in MDD and associated with current depression severity.

Dataset Information

Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression.

Publications

Altered gene synchrony suggests a combined hormone-mediated dysregulated state in major depression.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets